TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23010	69253;69254;69255	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
N2AB	21369	64330;64331;64332	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
N2A	20442	61549;61550;61551	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
N2B	13945	42058;42059;42060	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
Novex-1	14070	42433;42434;42435	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
Novex-2	14137	42634;42635;42636	chr2:178577307;178577306;178577305	chr2:179442034;179442033;179442032
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-128
• Domain position: 61
• Structural Position: 144
• Q(SASA): 0.1167
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/T	None	None	0.201	N	0.55	0.153	0.186928172975	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-06	0	0
A/V	rs1575830557	None	0.334	N	0.579	0.316	0.355034743287	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.546	ambiguous	0.4858	ambiguous	-1.523	Destabilizing	0.011	N	0.413	neutral	None	None	None	None	N
A/D	0.9769	likely_pathogenic	0.9787	pathogenic	-2.127	Highly Destabilizing	0.468	N	0.645	neutral	D	0.539799101	None	None	N
A/E	0.9698	likely_pathogenic	0.9712	pathogenic	-2.107	Highly Destabilizing	0.539	D	0.659	neutral	None	None	None	None	N
A/F	0.951	likely_pathogenic	0.9375	pathogenic	-1.238	Destabilizing	0.826	D	0.639	neutral	None	None	None	None	N
A/G	0.2789	likely_benign	0.316	benign	-1.435	Destabilizing	0.201	N	0.461	neutral	N	0.516668416	None	None	N
A/H	0.9781	likely_pathogenic	0.9748	pathogenic	-1.544	Destabilizing	0.947	D	0.613	neutral	None	None	None	None	N
A/I	0.649	likely_pathogenic	0.5169	ambiguous	-0.459	Destabilizing	0.7	D	0.661	neutral	None	None	None	None	N
A/K	0.9867	likely_pathogenic	0.9854	pathogenic	-1.356	Destabilizing	0.539	D	0.658	neutral	None	None	None	None	N
A/L	0.6449	likely_pathogenic	0.5731	pathogenic	-0.459	Destabilizing	0.25	N	0.607	neutral	None	None	None	None	N
A/M	0.7383	likely_pathogenic	0.6687	pathogenic	-0.527	Destabilizing	0.982	D	0.615	neutral	None	None	None	None	N
A/N	0.9021	likely_pathogenic	0.8982	pathogenic	-1.343	Destabilizing	0.539	D	0.654	neutral	None	None	None	None	N
A/P	0.8019	likely_pathogenic	0.7934	pathogenic	-0.647	Destabilizing	0.638	D	0.663	neutral	D	0.536604069	None	None	N
A/Q	0.9509	likely_pathogenic	0.9459	pathogenic	-1.486	Destabilizing	0.7	D	0.629	neutral	None	None	None	None	N
A/R	0.9701	likely_pathogenic	0.9688	pathogenic	-1.057	Destabilizing	0.7	D	0.651	neutral	None	None	None	None	N
A/S	0.1468	likely_benign	0.1483	benign	-1.703	Destabilizing	0.002	N	0.285	neutral	D	0.523789487	None	None	N
A/T	0.1675	likely_benign	0.1446	benign	-1.587	Destabilizing	0.201	N	0.55	neutral	N	0.511937697	None	None	N
A/V	0.2873	likely_benign	0.2013	benign	-0.647	Destabilizing	0.334	N	0.579	neutral	N	0.472314943	None	None	N
A/W	0.9956	likely_pathogenic	0.9941	pathogenic	-1.636	Destabilizing	0.982	D	0.617	neutral	None	None	None	None	N
A/Y	0.9801	likely_pathogenic	0.9769	pathogenic	-1.208	Destabilizing	0.826	D	0.641	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.